Open Label, Single Ascending Dose, Cross-over Study to Assess the Pharmacokinetics of Circadin® (Prolonged-Release Melatonin) Mini Tablets in Children With Neurodevelopmental Disorders and Sleep Disturbances
Overview
- Phase
- Phase 1
- Intervention
- Circadin 10 mg
- Conditions
- Sleep Problems
- Sponsor
- Neurim Pharmaceuticals Ltd.
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
There is increasing evidence that chronic sleep disorders in children with autism spectrum disorder (ASD), Angelman Syndrome (AS) and Smith-Magenis syndrome (SMS) are associated with disturbed melatonin secretion and melatonin administration has been shown to be effective in these populations. For children who have difficulties swallowing a tablet, Neurim has developed an age-appropriate Melatonin formulation in the form of mini-tablets which have the same dissolution profile as the Circadin® tablets product, thus should produce the same melatonin concentration-time profile with the same effects. This study concerns the pharmacokinetic study.
The purpose of this study is to :
- Establish the 24 hour baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
- Establish the concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
- Evaluate the adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject must be 2 to 17 years old
- •Subject has a documented history of autistic spectrum disorder (ASD; as confirmed according to, DSM-IV-TR 299.00, 299.10 and 299.80 or ICD 10: F 84.0, F84.2, F84.3, F84.5, F84.9 ) or one of the following neurogenetic diseases according to ICD 10: Smith-Magenis syndrome, Angelman syndrome or Tuberous Sclerosis (Bourneville's disease)
- •Subject has current sleep problems; defined as difficulty initiating or maintaining sleep, or non restorative sleep, for at least 1 month (DSM-IV 307.42). Subject is able to comply with taking the study drug and collaborate freely with the study procedures;
- •Written informed consent from parents having parental responsibility or from the legal guardian(s). In the case of a child is aged 12 years or older the written informed consent of the child is needed in addition to that of parents having responsibility/legal guardian;
- •Subject is able to understand instructions in Dutch.
Exclusion Criteria
- •Subject has history of difficulty with swallowing and/or easy choking;
- •Subject has current symptoms suggestive of obstructive sleep apnea syndrome or any breathing related sleep disorders or periodic limb movements;
- •Subject has known clinically significant disturbance(s) in hepatic and/or renal function;
- •Subject has non-stable epileptic attacks within 3 months prior to screening, in case of a history of epilepsy;
- •Subject who currently has asthmatic symptoms;
- •Subject has untreated medical/psychological condition that may be the etiology of sleep disturbances;
- •Subject is unable to refrain from the use of disallowed concomitant medication ordietary supplements (see paragraph 3.4) from 1 week prior to study occasions;
- •Subject is unable to refrain from caffeine-containing products for 24 hours before each occasion;
- •Subject has a known allergy to melatonin;
- •Female subject who is pregnant at time of screening;
Arms & Interventions
Circadin 10 mg
Second arm higher dose
Intervention: Circadin 10 mg
Circadin 2 mg
First arm lower dose
Intervention: Circadin 2 mg
Outcomes
Primary Outcomes
baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion
Time Frame: up to 1 year
To establish the 24 hour baseline profile of endogenous saliva melatonin concentrations and urine 6-SMT excretion in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration
Time Frame: up to 1 year
To establish the concentration-time profile of saliva melatonin concentrations and 24 hour 6-SMT urine excretion after 2 and 10 mg Circadin® mini-tablets single dose administration in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.
adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets
Time Frame: up to 1 year
To evaluate the adverse event profile after a single dose of 2 or 10 mg Circadin® mini-tablets in children aged 2 up to and including 17 years with neurodevelopmental disorders with sleep disturbances.